A review of the literature shows that there are eight previously-reported cases of paraneoplastic vitelliform retinopathy associated with metastatic cutaneous melanoma [4
] seven cases associated with metastatic choroidal melanoma, [5
] one case associated with metastatic visceral melanoma,  and two cases associated with metastatic melanoma with unknown primary source [7
]. There is one reported case of paraneoplastic vitelliform retinopathy associated with carcinoma in a patient with a history of breast and lung cancer but no sign of melanoma on systemic evaluation [19
Both of our cases were associated with cutaneous melanoma. As with all of the other reported cases of paraneoplastic vitelliform retinopathy, our cases were associated with metastatic disease. Most patients experience nyctalopia, though, as in our cases, they can experience other symptoms, such as decreased vision, haloes, photopsias, or metamorphopsia. All cases have been reported to be bilateral (except in patients whose fellow eye had previously been enucleated due to choroidal melanoma). Typical fundus findings show multifocal, yellow-orange vitelliform lesions beneath the neurosensory retina and at the level of the RPE. There is often associated subretinal fluid in the macula. Fluorescein angiography, which was performed in our second case, typically shows blockage without leakage in the areas of the vitelliform lesions. As with our cases, OCT can show multiple areas of subretinal fluid, as well focal deposits of hyper-reflective material overlying the RPE. EOG was performed in seven previously-reported cases, and of these cases, four reported abnormal Arden ratios, ranging from 1.1 to 1.7 [4
]. This is consistent with the EOG results of our second case.
Several of the previously-reported cases of vitelliform retinopathy associated with metastatic melanoma have demonstrated the presence of anti-retinal antibodies, supporting a paraneoplastic etiology [4
]. Two of these cases demonstrated anti-RPE antibodies [5
]. The first case showed a serum sample positive for autoantibodies against bestrophin-1, a 68 kDa RPE protein affected in Best macular dystrophy. However, genetic testing was not consistent with Best macular dystrophy, as it did not show any evidence of mutations in the VMD2 gene, which encodes the bestrophin-1 protein. The serum sample also showed a low titer of autoantibodies against α-enolase but not recoverin, which are commonly associated with cancer-associated retinopathy (CAR) [5
]. CAR is usually seen in patients with small-cell carcinoma of the lung. The second case showed a serum sample not only positive for MAR antibodies, but also positive for anti-RPE autoantibodies against peroxiredoxin 3 isoform b (PRDX3), a 26.1 kDa protein. This case also did not show any mutations in the VMD2 gene [18
]. Another case showed high serum titers of autoantibodies against carbonic anhydrase II (CAII), which is a 30-kDa protein present in the retina and RPE [4
]. Finally, one case showed serum autoantibodies against bipolar cells, which has been demonstrated in MAR [12
There is one report of the histopathology of vitelliform retinopathy associated with metastatic cutaneous melanoma. In this case, although there were no clinical signs of choroidal metastasis (via fundus examination, fluorescein angiography, or ultrasonography), histopathology revealed a flat, pigmented, cellular infiltrate composed of spindle-shaped and epithelioid cells in the choroid consistent with metastatic choroidal melanoma. Overlying the tumor were multiple, small RPE detachments. The authors argue that the histopathology in this case supports a local, subclinical metastasis as the cause of the vitelliform lesions rather than a paraneoplastic entity. Another proposed explanation was that the choroidal metastasis developed after the development of paraneoplastic vitelliform lesions [17
]. Our first case showed two clinically visible metastatic lesions, and whether the vitelliform lesions were present prior to choroidal metastases or developed as a result of the choroidal metastases is unclear.
Unfortunately, the presence of vitelliform retinopathy in a patient with metastatic melanoma is generally associated with a poor prognosis, with most patients succumbing to their metastatic disease. There is, however, a report of a patient who responded well to the oral treatment of his melanoma with the alkylating agent, temozolomide. Treatment of his systemic disease resulted in resolution of the subretinal fluid and improvement of visual acuity, though the vitelliform deposits still increased in size [18
As paraneoplastic vitelliform retinopathy is a rare condition, it is unknown at present whether any acquired vitelliform retinopathy should warrant a full neoplastic workup. However, this condition should be considered in any patient with vitelliform lesions and a history of prior malignancy, even if the malignancy was previously considered to be in remission. A thorough systemic evaluation should be performed for metastatic disease, and treatment is aimed at the underlying malignancy.